title: The role of intracellular pathways in the proliferation of human K562 cells mediated by muscarinic receptors.
abstract: Muscarinic acetylcholine receptors (mAChRs) are members of the superfamily of G protein coupled receptors (GPCRs). Muscarinic receptors are relatively abundant in the central nervous system and in the peripheral parasympathetic nervous system. Several studies have suggested that muscarinic receptors also mediate some cellular events in hematopoietic cells. K562 erythroleukemia cells contain muscarinic receptors M2, M3 and M4, and activation of muscarinic receptors changes cell proliferation. We examined the effects of several compounds on cell proliferation in K562 erythroleukemia cells. These included a muscarinic receptor agonist carbachol (CCh), a protein kinase inhibitor staurosporine; the phospholipase C inhibitor U73122, the MEK 1-2 inhibitor UO126, the PI3-kinase inhibitor wortmannin, the Ca(2+) chelators BAPTA/AM and 2-aminoethoxy-diphenylborate (2APB). In addition, we also investigated muscarinic receptor mediated protein kinase C (PKC) expression in K562 cells. CCh caused a decrease in DNA synthesis in K562 cells supplemented with 1% fetal bovine serum after starvation. Pre-treatment of K562 cells with U73122 and BAPTA/AM antagonized the inhibitory effect of CCh, suggesting that phospholipase C and intracellular calcium are involved in CCh-mediated inhibition of proliferation in K562 cells. Our data also suggest that the regulatory roles of protein kinase C and the MAPK/ERK pathways in K562 cell proliferation are independent of cholinergic activation.
authors.affiliation: Department of Biophysics, Marmara University School of Medicine, Istanbul, Turkey.
authors.forename: Banu
authors.initials: B
authors.lastname: Aydın
authors.forename: Beki
authors.initials: B
authors.lastname: Kan
authors.forename: Hulya
authors.initials: H
authors.lastname: Cabadak
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D018679:Cholinergic Agonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011760:Pyrrolidinones / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine / Q000494:pharmacology
chemical_list: D002070:Butadienes; D002118:Calcium; D002217:Carbachol; D018679:Cholinergic Agonists; D004791:Enzyme Inhibitors; D004963:Estrenes; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D009570:Nitriles; D019869:Phosphatidylinositol 3-Kinases; D010726:Phosphodiesterase Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D011760:Pyrrolidinones; D011976:Receptors, Muscarinic; D019311:Staurosporine; C113580:U 0126; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
keywords: Atropine; Carbachol; Cell signaling; Leukemia cell line; Muscarinic receptors; PKC